TNF-.ALPHA. augments the expression of RhoA in the rat bronchus

• Sakai Hiroyasu

  Department of Pharmacology, School of Pharmacy, Hoshi University

• Otogoto Shinobu

  Department of Pharmacology, School of Pharmacy, Hoshi University

• Chiba Yoshihiko

  Department of Pharmacology, School of Pharmacy, Hoshi University

• Abe Kazuho

  Department of Pharmacology, School of Pharmacy, Hoshi University

• Misawa Miwa

  Department of Pharmacology, School of Pharmacy, Hoshi University

Abstract

While nonspecific airway hyperresponsiveness (AHR) is a central feature of allergic bronchial asthma, the mechanism underlying the developmont of AHR is not clearly understood. We have previously demonstrated in vitro hyperresponsiveness of bronchial smooth muscle to acetylcholine (ACh) in rats that were actively sensitized and repeatedly challenged with aerosolized antigen. It has also been demonstrated that the ACh-induced, RhoA-mediated Ca²⁺ sensitization is markedly augmented concomitantly with an increased expression and activation of RhoA protein in the bronchial smooth muscle of the antigen-treated rats. In the present study, we have investigated whether TNF-α, a proinflammatory cytokine which is involved in bronchial asthma, causes upregulation of RhoA mRNA and protein in the rat bronchus. Treatment of rat bronchial smooth muscle preparations with TNF-α (300 ng/ml for 24 hr) significantly shifted the concentration-response curve to ACh upwards, but did not alter the response to high K⁺, when compared to that of control tissues. Levels of RhoA mRNA and protein in the TNF-α-treated bronchus were significantly greater than those in the control group. In conclusion, it is suggested that the augmentation of the ACh-induced contractile response evoked by TNF-α might be mediated by an upregulation of RhoA in rat bronchial smooth muscle.<br>

Journal

• Journal of Smooth Muscle Research

  Journal of Smooth Muscle Research 40 (1), 25-34, 2004

  Japan Society of Smooth Muscle Research

Keywords

• TNF-α
• airway hyperresponsiveness
• smooth muscle
• acetylcholine
• RhoA

Details

• CRID: 1390001205055978496
• NII Article ID: 110002912889
• NII Book ID: AN10364204
• DOI: 10.1540/jsmr.40.25
• ISSN: 18848796
• ISSN: 09168737
• PubMed: 15170075
• Web Site: http://www.jstage.jst.go.jp/article/jsmr/40/1/40_1_25/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2006047414
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
• Abstract License Flag: Disallowed